The concepts of gene therapy arose initially during the 1960s and early 1970s whilst the development of genetically marked cells lines and the clarification of mechanisms of cell transformation by the papovaviruses polyoma and SV40 was in progress. With the arrival of recombinant DNA techniques, cloned genes became available and were used to demonstrate that foreign genes could indeed correct genetic defects and disease phenotypes in mammalian cells in vitro. Efficient retroviral vectors and other gene transfer methods have permitted convincing demonstrations of efficient phenotype correction in vitro and in vivo, now making gene therapy a broadly accepted approach to therapy and justifying clinically applied studies with human patients.
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
Current advances in gene therapy of mitochondrial diseases
Journal of Translational Medicine Open Access 05 December 2022
Debutant iOS app and gene‐disease complexities in clinical genomics and precision medicine
Clinical and Translational Medicine Open Access 04 October 2019
Photo-thermal effects in gold nanorods/DNA complexes
Micro and Nano Systems Letters Open Access 12 October 2015
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Rent or buy this article
Get just this article for as long as you need it
Prices may be subject to local taxes which are calculated during checkout
Anderson, W.F. Prospects for human gene therapy. Science 226, 401–409 (1984).
Nichols, E.K. Gene therapy. (ed. Boyer, H.) (Harvard University Press, Cambridge, 1988).
Friedmann, T. Progress toward human gene therapy. Science 244, 1275–1281 (1989).
Verma, I.M. Gene therapy. Sci. Am. 263, 68–72 (1990).
Anderson, W.F. Human gene therapy. Science 256, 808–813 (1992).
Miller, A.D. Human gene therapy comes of age. Nature 357, 455–460 (1992).
Avery, O.T., McLeod, C.M. & McCarty, M. Studies on the chemical nature of the substance inducing transformation of pneumococcal types. J. exp. Med. 79, 137–158 (1944).
Szybalska, E.H. & Szybalski, W. Genetics of human cell lines, IV. DNA-mediated heritable transformation of a biochemical trait. Proc. natn. Acad. Sci. U.S.A 48, 2026–2034 (1962).
Seegmiller, J.E., Rosenbloom, F.M. & Kelly, W.N. Enzyme defect associated with a sex-linked human neurological disorder and excessive purine synthesis. Science 155, 1682–1684 (1967).
Kao, F.T. & Puck, T.T. Genetics of somatic mammalian cells: Induction and isolation of nutritional mutants in Chinese hamster cells. Proc. natn. Acad. Sci. U.S.A. 60, 1275–1281 (1968).
Borenfreund, E. & Bendich, A. A study of the penetration of mammalian cells by deoxyribonucleic acids. J. Biophys. Biochem. Cyt. 9, 81–91 (1961).
Kay, E.R.M. Incorporation of deoxyribonucleic acid by mammalian cells in vitro. Nature 191, 387–388 (1961).
Rabotti, G.F. Incorporation of DNA into a mouse tumor in vivo and in vitro. Exp. cell. Res. 31, 562–565 (1963).
Bradley, T.R., Roosa, R.A. & Law, L. DNA transformation studies with mammalian cells in culture. J. Cell. Comp. Physiol. 60, 127–138 (1962).
Majumdar, A. & Bose, S.K. DNA mediated genetic transformation of a human cancerous cell line cultured in vitro. Ind. J. med. Res. 603–612 (1968).
Bendich, A., Borenfreund, E. & Honda, Y. In DNA-induced heritable alteration of mammalian cells. 80–87 (North-Holland Publishing Company, 1971).
Hill, M. & Huppert, J. Fate of exogenous mouse DNA in chicken fibfoblasts in vitro: non-conservative preservation. Biochim. Biophys. Acta 213, 26–35 (1970).
Sambrook, J., Westphal, H., Srivansan, P.R. & Dulbecco, R. The integrated state of viral DNA in SV40-transformed cells. Proc. natn. Acad. Sci. U.S.A. 59, 1288–1293 (1968).
Hill, M. & Hillova, J. Virus recovery in chicken cells treated with Rous sarcoma cell DNA. Nature NBiol 237, 35–39 (1972).
Topp, W.C., Lane, D. & Pollack, R. Transformation by SV40 and polyoma virus in DNA Tumor Viruses (ed. Tooze, J. ) 205–296 (Cold Spring Harbor Press, Cold Spring Harbor, 1981).
Rogers, S. & Pfuderer, P. Use of viruses as carriers of added genetic information. Nature 219, 749–751 (1968).
Aposhian, H.V., Qasba, P.K., Osterman, J.V. & Waddell, A. Polyoma pseudovirions: An experimental model for the development of DNA for gene therapy. Fed. Proc. 31, 1310–1314 (1972).
Aposhian, H.V. The use of DNA for gene therapy: the need, experimental approaches and implications. Persp. biol. Med. 14, 98–108 (1970).
Friedmann, T. In vitro reassembly of shell-like particles from disrupted polyoma virus. Proc. natn. Acad. Sci. U.S.A. 68, 2574–2578 (1971).
Friedmann, T. & Roblin, R. Gene therapy for human genetic disease? Science 178, 648–649 (1972).
Rogers, S., Lowenthal, A., Terheggen, H.G. & Columbo, J.P. Induction of arginase activity with the Shope papilloma virus in tissue culture cells from an argininemic patient. J. exp. Med. 137, 1091–1096 (1973).
Changeux, JP. On the arginase of Shope papillomas. Virology 31, 729–732 (1967).
Terheggen, H.G., Lowenthal, A., Lavinha, F., Columbo, J.P. & Rogers, S. Unsuccesful trial of gene replacement in arginase deficiency. Z. Kinderheil. 119, 1–3 (1975).
Tatum, E.L. Molecular biology, nucleic acids and the future of medicine. Persp. biol. Med. 10, 19–32 (1966).
Davis, B.D. Prospects for genetic intervention in Man. Science 170, 1279–1283 (1970).
Sinsheimer, R. The prospect for designed genetic change. Ann. Surg. 57, 134–142 (1969).
The Prospects of Gene Therapy (ed. Freese, E. ) (Bethesda, Fogarty International Center, NIH, Bethesda, 1972).
Friedmann, T. & Roblin, R. Gene therapy for human genetic disease? Science 175, 949–955 (1972).
Jackson, D.A., Symons, R.H. & Berg, P. Biochemical method for inserting new genetic information into DNA of simian virus 40: Circular SV40 DNA molecules containing lambda phage genes and the galactose operon of Escherichia coli. Proc. natn. Acad. Sci. U.S.A. 69, 2904–2909 (1972).
Friedmann, T. The future for gene therapy: A re-evaluation. Ann. N. Y. Acad. Sci. 265, 141–152 (1976).
Morrow, J. The prospects for gene therapy in humans. Ann. N. Y. Acad. Sci. 265, 13–21 (1976).
Neville, R. Gene therapy and the ethics of genetic therapeutics. Ann. N. Y. Acad. Sci. 265, 153–169 (1976).
Maniatis, T., Jim, G.K., Efstradiadis, A. & Kafatos, F. Amplification and characterization of beta-globin gene synthesized in vitro. Cell 8, 163–182 (1976).
Graham, F.L. & Van der Eb, A.J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology 52, 456–467 (1973).
Wigler, M., Pellicer, A., Silverstein, S. & Axel, R. Transfer of single-copy eucaryotic genes using total cellular DNA as donor. Cell 14, 725–731 (1978).
Green, M.R., Treisman, R. & Maniatis, T. Transcriptional activation of cloned human beta-globin genes by viral immediate–early gene products. Cell 35, 137–148 (1982).
Mulligan, R.C., Howard, B.H. & Berg, P. Synthesis of rabbit beta-globin in cultured monkey kidney cells following infection with a SV40 beta-globin recombinant genome. Nature 277, 108–114 (1979).
Mulligan, R.C. & Berg, P. Selection for animal cells that express the Escherichia coli gene for xanthine-guanine phosphoribosyltransferase. Proc. natn. Acad. Sci. U.S.A. 78, 2072–2076 (1981).
Mulligan, R.C. & Berg, P. Factors governing the expression of a bacterial gene in mammalian cells. Molec. Cell. Biol. 1, 449–459 (1981).
Cline, M.J. et al. Gene transfer in intact animals. Nature 284, 422–425 (1980).
Mercola, K.E., Stang, H.D., Browne, J., Salser, W. & Cline, M.J. Insertion of a new gene of viral origin into bone marrow cells of mic. Science 208, 1033–1035 (1980).
Wade, N. Gene therapy pioneer draws Mikadoesque rap. Science 212, 1253 (1981).
Wade, N. Gene therapy caught in more entaglements. Science 212, 24–25 (1981).
Wade, N. UCLA gene therapy racked by friendly fire. Science 210, 509–511 (1980).
Anderson, W.F. & Fletcher, J.C. Gene therapy in human beings: When is it ethical to begin? New. Engl. J. Med. 303, 1293–1297 (1980).
Friedmann, T. Gene therapy: Fact and fiction. In Biology's New Approaches to Disease. (A Banbury Public Information Report, Cold Spring Harbor, 1983).
Temin, H.M. Mechanism of cell transformation by RNA tumor viruses. Ann. Rev. Med. 25, 609–649 (1971).
Temin, H.M. The DNA provirus hypothesis:the establishment and implications of RNA-directed DNA synthesis. Science 192, 1075–1080 (1976).
Temin, H.M. & Mizutani, S. RNA-directed DNA polymerase in virions of Rous sarcoma virus. Nature 226, 1211–1213 (1970).
Baltimore, D. RNA-dependent DNA polymerase in virions of RNA tumor viruses. Nature 226, 1209–1211 (1970).
Shimotohno, K. & Temin, H.M. Formation of infectious progeny virus after insertion of herpes simplex thymidine kinase gene into DNA of an avian retrovirus. Cell 26, 67–77 (1981).
Wei, C., Gibson, M., Spear, P.G. & Scolnick, E.M. Construction and isolation of a transmissible retrovirus containing the src gene from Harvey Murine Sarcoma Virus and the thymidine kinase gene from herpes simplex virus type 1. J. Virol. 39, 935–944 (1981).
Tabin, C.J., Hoffmann, J.W., Goff, S.P. & Weinberg, R.A. Adaptation of a retrovirus as a eucaryotic vector transmitting the herpes simplex thymidine kinase gene. Molec. cell. Biol. 2, 426–436 (1982).
Doehmer, J. et al. Introduction of rat growth hormone into mouse fibroblasts via a retroviral DNA vector. Proc. natn. acad. sci. U.S.A. 79, 2268–2272 (1982).
Miller, A.D., Law, M.F. & Verma, I. Generation of helper-free amphotropic retroviruses that transduce a dominantacting, methotrexate-resistant dihydrofolate reductase gene. Molec. cell. Biol. 5, 431–437 (1985).
Miller, A.D. & Buttimore, C. Redesign of retrovirus packaging lines to avoid recombination leading to helper virus production. Molec. cell. Biol. 6, 2895–2902 (1986).
Mann, R., Mulligan, R.C. & Baltimore, D. Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus. Cell 33, 153–159 (1983).
Markowitz, D., Goff, S. & Bank, A. A safe packaging line for gene transfer: Separating viral genes on two different plasmids. J. Virol. 62, 1120–1124 (1988).
Temin, H.M. Retrovirus vectors for gene transfer: Efficient integration into and expression of exogenous DNA in vertebrate cell genomes. In Gene Transfer (ed. Kucherlapati, R.) 149–187 (Plenum Press, New York, 1986).
Jolly, D.J. et al. Isolation and characterization of a full-length expressible cDNA for human hypoxanthine phosphoribosyltransferase. Proc. natn. Acad. Sci. U.S.A. 80, 477–481 (1983).
Miller, A.D., Jolly, D.J., Friedmann, T. and Verma, I.M. A transmissible retrovirus expressing human hypoxanthine phosphoribosyltransferase (HPRT): Gene transfer into cells obtained from humans deficient in HPRT. Proc. natn. Acad. Sci. U.S.A. 80, 4709–4713 (1983).
Willis, R.C. et al. Partial phenotypic correction of human Lesch-Nyhan (hypoxanthine-guanine phosphoribosyltransferase-deficient) lymphoblasts with a transmissible retroviral vector. J. biol. Chem. 259, 7842–7849 (1984).
Kantoff, P.W. et al. Correction of adenosine deaminase deficiency in cultured human T and B cells by retrovirus-mediated gene transfer. Proc. natn. Acad. Sci. U.S.A. 83, 6563–6567 (1986).
Selden, R.F., Skoskiewicz, M.J., Howie, K.B., Russell, P.S. & Goodman, H.M. Implantation of genetically engineered fibroblasts into mice: Implications for gene therapy. Science 236, 714–718 (1987).
Garver, R.I., Jr., Chytil, A., Courtney, M. and Crystal, R.G. Clonal gene therapy: Transplanted mouse fibroblast clones express human alphal-antitrypsin gene in vivo. Science 237, 762–764 (1987).
Palmer, T.D., Hock, R.A., Osborne, W.R.A. & Miller, A.D. Efficient retrovirus mediated transfer and expression of a human adenosine deaminase gene in diploid skin fibroblasts from an adenosine deaminase-deficient human. Proc. natn. Acad. Sci. U.S.A. 84, 1055–1059 (1987).
St Louis, D. & Verma, I.M. An alternative approach to somatic cell gene therapy. Proc. natn. Acad. Sci. U.S.A. 85, 3150–3154 (1988).
Rosenberg, M.B. et al. Grafting genetically modified cells to the damaged brain: Restorative effects of NGF expression. Science 242, 1575–1578 (1988).
Wolff, J.A. et al. Grafting fibroblasts genetically modified to produce L-dopa in a rat model of Parkinson disease. Proc. natn. Acad. Sci. U.S.A. 86, 9011–9014 (1989).
Miller, A.D., Eckner, R.J., Jolly, D.J., Friedmann, T. & Verma, I.M. Expression of a retrovirus encoding human HPRT in mice. Science 225, 630–632 (1984).
Williams, D.A., Lemischka, I.R., Nathan, D.G. & Mulligan, R.C. Introduction of new genetic material into pluripotent haematopoietic stem cells of the mouse. Nature 310, 476–480 (1984).
Gruber, H. et al. Retroviral vector-mediated gene transfer into human hematopoietic cells. Science 230, 1057–1061 (1985).
Williams, D.A., Orkin, S.H. & Mulligan, R.C. Retrovirus-mediated transfer of human adenosine deaminase gene sequences into cells in culture and into murine haematopoietic cells in vivo. Proc. natn. Acad. Sci. U.S.A. 83, 2566–2570 (1986).
Wolff, J.A. et al. Expression of retrovirally transduced genes in primary cultures of adult rat hepatocytes. Proc. natn. Acad. Sci. U.S.A. 84, 3344–3348 (1987).
Ledley, F.D., Darlington, G.J., Hahn, T. & Woo, S.L.C. Retroviral gene transfer into primary hepatocytes: Implications for genetic therapy of liver-specific functions. Proc. natn. Acad. Sci. U.S.A. 84, 5335–5339 (1987).
Morgan, J.R., Barrandon, Y., Green, H. & Mulligan, R.C. Expression of an exogenous growth hormone gene by transplantable human epidermal cells. Science 237, 1476–1479 (1987).
Salminen, A., Elson, H.F., Mickley, L.A., Fojo, A.F. & Gottesman, M.M. Implantation of recombinant rat myoblasts into adult skeletal muscle: potential gene therapy. Hum. gene Ther. 2, 15–26 (1991).
Barr, E. & Leiden, J.M. Systemic delivery of recombinant proteins by genetically modified myoblasts. Science 254, 1507–1509 (1991).
Dhawan, J. et al. Systemic delivery of human growth hormone by injection of genetically engineered myoblasts. Science 254, 1509–1512 (1991).
Nabel, E.G., Plautz, G., Boyce, F.M., Stanley, J.C. & Nabel, G.J. Recombinant gene expression in vivo within endothelial cells of the arterial wall. Science 244, 1342–1344 (1989).
Wilson, J.M. et al. Implantation of vascular grafts lined with genetically modified endothelial cells. Science 244, 1344–1346 (1989).
Nabel, E.G., Plautz, G. & Nabel, G.J. Site-specific expression in vivo by direct gene transfer into the arterial wall. Science 249, 1285–1288 (1990).
Rosenfeld, M.A. et al. In vivo transfer of the human cystic fibrosis transmembrane conductance regulator gene to the airway epithelium. Cell 68, 143–155 (1992).
Fletcher, J.C. Moral problems and ethical issues in prospective human gene therapy. Virginia Law Review 69, 515–546 (1983).
Editorial, Gene therapy in man. Recommendation of European medical research councils. Lancet 1, 1271–1272 (1988).
Anderson, W.F. Human gene therapy: Why draw a line? J. med. Philos. 14, 681–693 (1989).
Friedmann, T. HPRT gene transfer as a model for gene therapy. In Genetic Engineering—Principles and Methods, Vol. 7 (eds. Setlow, J. & Hollaender, A. ) 263–282 (Plenum Press, New York, 1985).
Giblett, E.R., Anderson, J.E., Cohen, F., Pollara, B. & Meuwissen, H.J. Adenosine deaminase deficiency in two patients with severely impaired cellular immunity. Lancet 2, 1067–1069 (1972).
van Beusechem, V.W. et al. Expression of human adenosine deaminase in mice transplanted with hemopoietic stem cells infected with amphotropic retroviruses. J. Exp. Med. 172, 729–736 (1990).
Ferrari, G. et al. An in vivo model of somatic cell gene therapy for human severe combined immunodeficiency. Science 251, 1363–1366 (1991).
Miyanohara, A., Sharkey, M.F., Witztum, J.L., Steinberg, D. & Friedmann, T. Efficient expression of retroviral vector-transduced human low density lipoprotein (LDL) receptor in LDL receptor-deficient rabbit fibroblasts in vitro. Proc. natn. Acad. Sci. U.S.A. 85, 6538–6542 (1988).
Chowdhury, J.R. et al. Long-term improvement of hypercholesterolemia after ex vivo gene therapy in LDLR–deficient rabbits. Science 254, 1802–1805 (1991).
Ledley, F.D. & Woo, S.L. Molecular basis of alpha1-antitrypsin deficiency and its potential therapy by gene transfer. J. Inher. metab. Dis. 9, supp. 1, 85–91 (1989).
Rosenfeld, M.A. et al. Adenovirus-mediated transfer of a recombinant a1-antitrypsin gene to the lung epithelium in vivo. Science 252, 431–434 (1991).
Kay, M.A. et al. Expression of human a1-antitrypsin in dogs after autologous transplantation of retroviral transduced hepatocytes. Proc. natn. Acad. Sci. U.S.A. 89, 89–93 (1992).
Palmer, T.D., Thompson, A.R. & Miller, A.D. Production of human factor IX in animals by genetically modified skin fibroblasts: Potential therapy for hemophilia B. Blood 73, 438–445 (1989).
Axelrod, J.H., Brinskhous, K.M. & Verma, I.M. Phenotypic correction of factor IX deficiency in skin fibroblasts of hemophilic dogs. Proc. natn. Acad. Sci. U.S.A. 87, 5173–5177 (1990).
Roman, M. et al. Circulating human or canine factor IX from retrovirally transduced primary myoblasts and established myoblast cell lines grafted into murine skeletal muscle. Somat. Cell molec. Genet. (in the press).
Miyanohara, A., Johnson, P.A., Elam, R.L. et al. Direct gene transfer to the liver with herpes simplex virus type 1 vectors: Transient production of physiologically relevant levels of circulating factor IX. New. Biol. 4, 238–246 (1992).
Yao, S.-N., Wilson, J.M., Nabel, E.G., Kurachi, S., Hachiya, H.L. & Kurachi, K. Expression of human factor IX in rat capillary endothelial cells: Toward somatic gene therapy for hemophilia B. Proc. natn. Acad. Sci. U.S.A. 88, 8101–8105 (1991).
Beutler, E. Gaucher disease: New molecular approaches to diagnosis and treatment. Science 256, 794–799 (1992).
Levine, F. & Friedmann, T. Gene therapy techniques. Curr. Opin. Biotech. 2, 840–844 (1992).
Felgner, P.L. et al. Lipofection: A highly efficient, lipid-mediated DNA-transfer procedure. Proc. natn. Acad. Sci. U.S.A. 84, 7413–7417 (1987).
Keating, A. & Toneguzzo, F. Gene transfer by electroporation: a model for gene therapy. Prog. Clin. biol. Res. 333, 491–498 (1990).
Wolff, J.A. et al. Direct gene transfer into mouse muscle in vivo. Science 247, 1465–1468 (1990).
Acsadi, G. et al. Human dystrophin expression in mdx mice after intramuscular injection of DNA constructs. Nature 352, 815–818 (1991).
Berkner, K.L. Development of adenovirus vectors for the expression of heterologous genes. Bio Techniques 6, 616–629 (1988).
Sczakiel, G., Pawlita, M. & Kleinheinz, A. Specific inhibition of human immunodeficiency virus type 1 replication by RNA transcribed in sense and antisense orientation from the 5′-leader/gag region. Biochem. Biophys. Res. Commun. 169, 643–651 (1990).
Levrero, M., Barban, V., Manteca, S., et al. Defective and nondefective adenovirus vectors for expressing foreign genes in vitro and in vivo. Gene 101, 195–202 (1991).
McLaughlin, S.K., Collis, P., Hermonat, P.L. & Muzyczka, N. Adeno-associated virus general transduction vectors: Analysis of proviral structures. J. Virol. 62, 1963 (1988).
Spaete, R.R. & Frenkel, N. The herpes simplex virus amplicon: a new eukaryotic defective-virus cloning-amplifying vector. Cell 30, 295–304 (1982).
Tackney, C., Cachianes, G. & Silverstein, S. Transduction of the Chinese hamster ovary aprt gene by herpes simplex virus. J. Virol. 52, 606–614 (1984).
Geller, A.I. & Breakefield, X.O. A defective HSV-1 vector expresses Escherichia coli b-galactosidase in cultured peripheral neurons. Science 241, 1667–1669 (1988).
Chiocca, E.A. et al. Transfer and expression of the lacZ gene in rat brain neurons mediated by herpes simplex virus mutants. New Biol. 2, 739–746 (1990).
Dobson, A.T., Margolis, T.P., Sedarati, F., Stevens, J.G. & Feldman, L.T. A latent, nonpathogenic HSV-1-derived vector stably expresses b-galactosidase in mouse neurons. Neuron 5, 353–360 (1990).
Johnson, P.A., Miyanohara, A., Levine, F., Cahill, T. & Friedmann, T. Cytotoxicity of a replication defective mutant of herpes simplex virus type 1. J. Virol. 66, 2952–2965 (1992).
Gansbacher, B. et al. Interleukin 2 gene transfer into tumor cells abrogates tumorigenicity and induces protective immunity. J. exp. Med. 172, 1217–1224 (1990).
Gansbacher, B. et al. Retroviral vector-mediated gamma-interferon gene transfer into tumor cells generates potent and long lasting antitumor immunity. Cancer Res. 50, 7820–7825 (1990).
Golumbeck, P.T. et al. Treatment of established renal cancer by tumor cells engineered to secrete interleukin-4. Science 254, 713–716 (1991).
Esumi, N., Hunt, B., Itaya, T. & Frost, P. Reduced tumorigenicity of murine tumor cells secreting gamma-interferon is due to non-specific host responses and is unrelated to class I major histocompatibility complex expression. Cancer Res. 51, 1185–1189 (1991).
Cheng, J., Yee, J.-K., Yeargin, J., Friedmann, T. & Haas, M. Suppression of acute lymphoblastic leukemia by the human wild-type p53 gene. Cancer Res. 52, 222–226 (1992).
Casey, G., Lo-Hsueh, M., Lopez, M.E., Vogelstein, B. & Stanbridge, E.J. Growth suppression of human breast cancer cells by the introduction of a wild-type p53 gene. Oncogene 6, 1791–1797 (1991).
Chen, Y., Chen, P.-L., Arnaiz, N., Goodrich, D. & Lee, W.-H. Expression of wild-type p53 in human A673 cells suppresses tumorigenicity but not growth rate. Oncogene 6, 1799–1805 (1991).
Tanaka, K. et al. Suppression of tumorigenicity in human colon carcinoma cells by introduction of normal chromosomes 5 or 18. Nature 349, 340–342 (1991).
Uzvolgyi, E. et al. Reintroduction of a normal retinoblastoma gene into retinoblastoma and osteosarcoma cells inhibits the replication-associated function of SV40 large T antigen. Cell Growth Diff. 2, 297–303 (1991).
Gage, F.H. et al. Grafting genetically modified cells to the brain: Possibilities for the future. Neuroscience 23, 795–807 (1987).
Huber, B.E., Richards, C.A. & Krenitsky, T.A. Retroviral-mediated gene therapy for the treatment of hepatocellular carcinoma: An innovative approach for cancer therapy. Proc. natn. Acad. Sci. U.S.A. 88, 8039–8043 (1991).
Culver, K.W. et al. In vivo gene transfer with retroviral vector-producing cells for treatment of experimental brain tumors. Science 256, 1550–1552 (1992).
Young, J.A.T., Bates, P., Willert, K. & Varmus, H.E. Efficient incorporation of human CD4 protein into avian leukosis virus particles. Science 250, 1421–1423 (1990).
Weerasinghe, M., Liem, S.E., Asad, S., Read, S.E. & Joshi, S. Resistance to human immunodeficiency virus type 1 infection in human CD4+ lymphocyte–derived cell lines conferred by using retroviral vectors expressing HIV-1 RNA-specific ribozyme. J. Virol. 65, 5531–5534 (1991).
Mitsuyama, H., Yarchian, R., Kageyama, S. & Broder, S. Targeted therapy of HIV-related disease. FASEB 5, 2369–2381 (1991).
Harrison, G.S. et al. Activation of a diphtheria toxin A gene by expression of human immunodeficiency virus type 1 Tat and Rev proteins in transfected cells. Hum. Gene Ther. 2, 53–60 (1001).
Venbatesh, L.K., Arens, M.Q., Subramanian, T. & Chinnedurai, G. Selective induction of toxicity to human cells expressing human immunodeficiency virus type 1 Tat by a conditionally cytotoxic adenovirus vector. Proc. natn. Acad. Sci. U.S.A. 87, 8746–8750 (1990).
Matthews, T.J., Langlois, A.J., Butto, S., Bolognesi, D.P. & Javaherian, K. HIV-neutralizing antibody and approaches to the envelope diversity problem. Adv. Exper. med. Biol. 303, 23–26 (1991).
Bolognesi, D.P. AIDS vaccines: Progress and unmet challenges. Ann. Intern. Med. 114, 161–162 (1991).
Rights and permissions
About this article
Cite this article
Friedmann, T. A brief history of gene therapy. Nat Genet 2, 93–98 (1992). https://doi.org/10.1038/ng1092-93
This article is cited by
Current advances in gene therapy of mitochondrial diseases
Journal of Translational Medicine (2022)
Gendoping und molekulares Doping
Advances in Inner Ear Therapeutics for Hearing Loss in Children
Current Otorhinolaryngology Reports (2020)
Debutant iOS app and gene‐disease complexities in clinical genomics and precision medicine
Clinical and Translational Medicine (2019)
Photo-thermal effects in gold nanorods/DNA complexes
Micro and Nano Systems Letters (2015)